This report describes mitochondrial complex I deficiency, nuclear type 17 (MC1DN17); MC1DN17 exhibits autosomal recessive inheritance. The human gene implicated in this disease subtype is NDUFAF6, a nuclear gene that is involved in the assembly of NADH:ubiquinone oxidoreductase (complex I), the first enzyme complex in the mitochondrial electron transport chain. There is a single fly ortholog, Dmel\sicily, for which for which classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
A UAS construct of the wild-type human Hsap\NDUFAF6 gene has been introduced into flies. Heterologous rescue (functional complementation) is observed: expression of the human gene rescues most of the phenotypes of an amorphic allele of Dmel\sicily.
Amorphic mutations of Dmel\sicily are recessive lethals; somatic clones exhibit neurophysiology defects. Genetic and physical interactions of sicily have been described; see below and in the FlyBase gene report for sicily.
[updated Apr. 2019 by FlyBase; FBrf0222196]
Mitochondrial complex I deficiency causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, and liver disease. [from MIM:252010; 2016.08.12]
[MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 17; MC1DN17](https://omim.org/entry/618239)
[NADH DEHYDROGENASE (UBIQUINONE) COMPLEX I, ASSEMBLY FACTOR 6; NDUFAF6](https://omim.org/entry/612392)
Mitochondrial complex I deficiency nuclear type 17 (MC1DN17) is caused by homozygous or compound heterozygous mutation in the nuclear-encoded NDUFAF6 gene. [from MIM:618239; 2019.04.24]
NDUFAF6 encodes a protein that localizes to mitochondria and plays a role in the assembly of complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain. Mutations in this gene are associated with complex I enzymatic deficiency. [from GeneCards, NDUFAF6; 2016.01.06]
One to one: 1 human to 1 Drosophila (reciprocal best hit).
High-scoring ortholog of human NDUFAF6 (1 Drosophila to 1 human). Dmel\sicily shares 43% identity and 62% similarity with human NDUFAF6.
